Friday, May 17, 2013

Where does it hurt? How bad does it hurt? Why does it hurt? The many inconsistent and inadequate ways of sorting chronic pain by anatomy, severity, and associated medical conditions are impeding the health and well-being of patients, optimal medical care, and treatment advances, say pain experts who are calling for a change.

One, the International Association for the Study of Pain (IASP) Classification of Pain Diseases Task Force, is working under the auspices of the World Health Organization (WHO) to generate the first chapter dedicated to pain for the next revision of the International Classification of Diseases (ICD). The other springs from the work of the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) public-private partnership and the American Pain Society (APS) to create a comprehensive evidence-based taxonomy of acute and chronic pain conditions that reflects the latest data on symptom patterns, comorbidities, and pathophysiologic mechanisms.

The independent initiatives share a similar broad goal to improve the understanding and treatment of pain through a comprehensive, structured framework that incorporates emerging science about the underlying biology and other factors. The projects also signal a growing acceptance of pain as a condition and specialty area of its own, on a par with fields such as infectious diseases, cancer, and cardiovascular disorders.

Several pain experts consulted for this story observed that new, comprehensive pain diagnostic criteria will have to grapple with many tough issues, including pressures to introduce new diagnoses or retain old ones, the complexities of pain symptoms and mysteries of etiology, a growing concern about the medicalization and overtreatment of normal human variation, and the tensions between lumping disorders into bigger groups for ease of general primary care and drug marketing or splitting them into fine distinctions more amenable to specialist care and personalized medicine.

Ideally, a new classification system will emphasize the mechanisms of pain over the location in the body, time course, and etiology, said Clifford Woolf, a neurobiologist at Boston Children's Hospital and Harvard Medical School, Massachusetts, US, who is not involved with either effort. "We're in a transition now that people realize that broad definitions, such as neuropathy, may encompass 20 different mechanistic bases," he said. "The quest is how to capture this. Can we define pain in such a way as to inform rational therapeutic decisions?"

Neither team can offer many concrete details, they said, because they are in the early consensus-building process about how best to organize the information and work. Both teams anticipate much vigorous debate, and plan to offer opportunities for pain experts and others to review and comment on draft classification schemes. Neither group specified a mechanism for consensus beyond the involvement of people who have participated in other classification processes related to pain and mental disorders. "In two years, I will be more talkative," said Rolf-Detlef Treede, a neurobiologist at the University of Heidelberg, Germany, and co-chair of the IASP task force.

A new ICD chapter for pain

On 13 March 2013, the IASP task force launched with a meeting of about 10 people in Frankfurt, Germany. The immediate priority is to develop appropriate chronic pain codes so indications can be recognized, specific treatments administered, doctors reimbursed, and patients counted, Treede said.

Last summer, the WHO gave the IASP task force the green light for a comprehensive revision of pain diagnosis in all medical fields, including psychiatry. For the first time, pain will have its own chapter in the health information standard used by most of the world to define diseases and study disease patterns, manage healthcare, monitor outcomes, and allocate resources. The updated ICD-11 is slated for release in 2015.

"The role of a diagnostic and classification system cannot be overestimated," said Winfried Rief, a clinical psychologist at the University of Marburg in Germany and co-chair of the IASP task force. "It is important for many decisions that will have consequences for the care of a single person who suffers from pain now and in 10 or 20 years, because the dissemination of research money depends on the diagnosis and classification process."

Nanna Finnerup, a neuroscientist at the Danish Pain Research Center at Aarhus University concurs. About 5 to 8 percent of the general population suffers from chronic neuropathic pain, she said. Yet, there is no ICD-10 code for most neuropathic conditions, even one as common as painful diabetic neuropathy. "It doesn't reflect the epidemiology and the distinct diagnostic and therapeutic requirements for neuropathic pain," she said.

In a kind of pilot demonstration of the ICD-11 revision, Treede and Rief helped introduce the multimodal pain code F45.41 into the German version of the ICD-10 in 2009, said Treede, who was president of the German pain society at the time. The change effectively allows patients with somatic chronic pain to access mental health treatment as part of multidisciplinary care, even if the causal source of the pain is not psychological. The change reflects recent evidence that shows a measurable influence of psychological and behavioral strategies in pain-related outcomes. This year, the German government approved coverage within the national health system to the insurance companies. It's too early to judge if that money is flowing to doctors, Treede said.

Rewriting the IASP book

With its bridge of biomedical and psychological factors, the German pain code change illustrates one of the complexities of classifying pain. "Pain is a complicated system," Rief said. "It can accrue in every body system and every body site. Pain classification needs a multidisciplinary approach."

The ICD-11 pain chapter may incorporate elements of the current IASP classification of chronic pain (originally published in 1986, with a second edition published in 1994 and selected updates in 2011 and 2012) and will eventually replace it with a new reference volume. "Despite its systematic approach, this classification has never been widely employed, even by pain specialists," observed Finnerup, Rief, Treede, and their colleagues in a recent paper calling for a new classification of neuropathic pain (Finnerup et al., 2013).

The IASP effort will be constrained by the fixed structure of the ICD, the WHO requirements for developing and validating ICD diagnoses, and by the need to be relevant to the diverse range of health systems and cultures around the world, Rief said. The first steps include collecting all the pain diagnoses in the different medical fields that form the organizing pillars of the ICD, such as cancer and musculoskeletal diseases. The task force and its working groups will try to harmonize the classification process and then tackle whether to introduce a new diagnosis, such as neuropathic pain, or modify an existing one, such as psychogenic pain.

The task force will fold in other diagnostic schemes that have emerged in specialty pain areas. For example, Rief cited the headache field's systematic hierarchical classification system and associated explicit diagnostic criteria that have dominated and revolutionized research, healthcare, and clinical practice for 20 years. The third edition of the International Classification of Headache Disorders (ICHD-3) is due out this year. The complicated and comprehensive list of 200 headache types is not feasible for the routine clinical practice in many parts of the world, but the headache experts "already have good ideas" about how to adapt their system in concert with the pain overhaul of ICD-11, Rief said.

"We want to improve the classification in general and to make it simple enough for the primary care physician who deals with thousands of diagnostic algorithms" in the ICD, Rief said. "It should be equally suitable in Nigeria and China."

Starting fresh

Independently, the ACTTION partnership came to a similar conclusion about the need for a comprehensive evidence-based taxonomy of acute and chronic pain, and last October announced on their website that they would partner with the American Pain Society (APS) "to establish a coordinated framework for pain diagnosis and classification, to provide evidence-based diagnostic criteria for the major acute and chronic pain conditions, and to broadly disseminate the pain classification and taxonomy so that it will have the greatest impact."

The leaders of the effort are reluctant to discuss the initiative in advance of the first meeting, which is scheduled for 17-18 May 2013. About 40 clinical researchers and government health officials have been invited to Washington, DC, to come up with a guiding framework, and to set up working groups and a timeline for classification and diagnostic criteria, starting with chronic pain.

The co-chairs of the May meeting cited both the research and clinical payoffs from standardized diagnostic criteria. The envisioned taxonomy will ensure consistent and accurate diagnoses in clinical research and clinical trials, they said. It will enable comparisons across studies for systematic reviews and meta-analyses, and assist regulatory review of new drug applications. "There is no systematic, constructive approach to pain classification," said co-chair Roger Fillingim, a psychologist at the University of Florida College of Dentistry, Gainesville, US, and APS president. "We would like to fill that gap."

As a model of success, co-chair Robert Dworkin, University of Rochester School of Medicine and Dentistry in New York, pointed to the transformative influence of the headache classification and the third edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III), published in 1980 by the American Psychiatric Association. The latest revision, the DSM-5, is scheduled for release in May (Kupfer et al., 2013).

"In 1980, DSM-III revolutionized psychiatry and brought it into the modern era," said Dworkin. "Pain doesn't have anything analogous."

The other leaders of the ACTTION-APS effort include Dennis Turk, a psychologist, and John Loeser, a neurosurgeon, both at the University of Washington in Seattle, US.

The biological and psychosocial mechanisms of pain are of particular interest to the group, because of the potential to identify treatments that will target similar underlying processes in otherwise distinct pain conditions. Dworkin, in particular, wants to address a situation that arose three years ago, when Eli Lilly sought to expand the approved uses of Cymbalta™ (duloxetine) to chronic pain generally. The U.S. Food and Drug Administration (FDA) turned to leading academic experts in pain medicine for scientific insight. Could a drug approved for diabetic neuropathy and fibromyalgia with new evidence of efficacy in low back pain and osteoarthritis now be presumed to work for the many varied types of pain sometimes lumped together as chronic? How broadly could the evidence of efficacy in the treatment of these four chronic pain conditions be extrapolated to other conditions? And what is chronic pain, anyway?

Unable to get solid answers from the academics, the FDA "had to figure it out on [their] own," said Dworkin. "It was pretty disappointing that there was such limited information relevant to lumping versus splitting chronic pain conditions." The FDA gave a limited green light to expand the drug's marketing to "management of chronic musculoskeletal pain," citing a lack of sound data about the mechanisms of pain and of analgesic drug action in patients with a variety of painful conditions.

Dworkin and his ACTTION-APS colleagues will have more to say about how to approach these questions after the May meeting. Stay tuned.

Carol Cruzan Morton covers science, health, and the environment, and is based near Boston, Massachusetts.